Immunosuppressive Drug Therapy

Immunosuppression is characterized by the reduction in the effectiveness of the immune system’s response to foreign substances. This can be the result of diseases such as AIDS and cancer, or therapies including immunosuppressive drugs, radiation or splenectomy.1

The treatment of non-autoimmune diseases such as the long-term control of allergic asthma

Immunosuppressive drugs form the mainstay of treatment following organ transplantation, ensuring long-term graft survival and improving the overall success rate of transplantation. ISD therapy is administered mainly during three phases after transplantation:

Maintenance - the phase after the acclimatization of the transplanted organ in the recipient

Reversal of established rejection3

Classification of ISDs4The drugs commonly used to suppress the immune system are classified into several categories based on mechanism of action as shown in the table below.

Category

Types

Example

Immunophilin-binding drugs

Calcineurin inhibitors

Cyclosporine A, tacrolimus

Non-inhibitors of calcineurin

Sirolimus

Anti-metabolites

Inhibitors of de novo purine synthesis

Mycophenolic acid (MPA) Mycophenolate ofetil (MMF), azathioprine

Inhibitors of de novo pyramidine synthesis

Leflunomide

Biologic immunosuppression

Polyclonal antibodies

Anti-thymocyte gamma globulin thymoglobulin

Monoclonal antibodies

Anti-CD3 monoclonal antibody (OKT3), IL-2H (humanized)

Others

Deoxyspergualin, corticosteroids, fingolimod (FTY720)

Recent Trends in Immunosuppression Immunosuppressive therapy has changed considerably over the past few decades with the introduction of new drugs and development of different drug regimens. The changing trends for optimizing transplantation management include:

Multi-regimen therapies

Calcineurin inhibitor (CNI) minimization regimens

Calcineurin inhibitor avoidance regimens

ISD Monitoring Rejection can occur any time post transplantation, and hence the lifelong administration of ISDs is usually required. The treatment regimen necessitates the regular monitoring and regulation of ISD doses in order to prevent probable rejection events and major adverse effects associated with supratherapeutic and subtherapeutic drug levels.

Need for ISD Monitoring

Some of the common techniques adopted for therapeutic drug monitoring (TDM) include the following:

1. Trough concentration monitoring (C0): In this method, the drug level that is reached prior to the administration of the subsequent dose is measured. One of the main drawbacks of this technique is that it provides just an approximate estimate of the drug levels during the dosing interval.5 The advantage of C0 monitoring, however, is that it requires only one sample, eliminating the need for patients to wait in the hospital, clinic, or physician office for multiple samples to be drawn.